Neuregulin 1 improves glucose tolerance in adult and old rats - 22/09/15

Doi : 10.1016/j.diabet.2015.08.003

K. Caillaud ^a,^b, N. Boisseau ^a,^b, G. Ennequin ^a,^b, V. Chavanelle ^a,^b, M. Etienne ^a,^b, X. Li ^c, P. Denis ^b,^d, D. Dardevet ^b,^d, A. Lacampagne ^e, P. Sirvent ^a,^b,^⁎
^a Université Clermont-Auvergne, université Blaise-Pascal, EA 3533, laboratoire des adaptations métaboliques à l’exercice en conditions physiologiques et pathologiques (AME2P), BP 80026, 63171 Aubière cedex, France
^b CRNH-Auvergne, 63001 Clermont-Ferrand, France
^c Zensun Sci & Tech Ltd., Shanghai, China
^d INRA, UMR1019, unité de nutrition humaine, 63000 Clermont-Ferrand, France
^e CHRU Montpellier, U1046 INSERM, UMR CNRS 9214, université de Montpellier, 34295 Montpellier, France

^⁎Corresponding author at: Université Blaise-Pascal, laboratoire des adaptations métaboliques à l’exercice en conditions physiologiques et pathologiques (AME2P), bâtiment Biologie B, 24, avenue des Landais, BP 80026, 63171 Aubière cedex, France Tel.: +00 33 4 73 40 71 33; fax: +00 33 4 73 40 50 62.

En prensa. Pruebas corregidas por el autor. Disponible en línea desde el Tuesday 22 September 2015
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Abstract

Aim

Studies both in vitro and ex vivo of rodent skeletal muscle have highlighted the potential involvement of neuregulin 1 (NRG1) in glucose metabolism regulation, yet nothing is known of the role of NRG1 in systemic glucose homoeostasis. For this reason, it was hypothesized that systemic delivery of NRG1 might improve glucose tolerance and that the effect might be age-dependent.

Methods

Glucose tolerance tests were performed in 6-month-old (adult) and 22-month-old (old) male Wistar rats 15min after a single injection of either NRG1 (50μg/kg) or saline (controls). Skeletal muscle and liver samples were also collected 30min after the acute NRG1 or saline treatment, while the phosphorylation status of ErbB receptors and AKT was assessed by Western blotting.

Results

Acute NRG1 treatment decreased the glycaemic response to an oral glucose load in both adult and old rats. NRG1 injection did not activate ErbB receptors in skeletal muscle, whereas phosphorylation of ErbB3 and AKT was markedly increased in the liver of NRG1-treated adult and old rats compared with controls.

Conclusion

This study shows that NRG1 has a possible glucose-lowering effect in the liver and via an ErbB3/AKT signaling pathway. This NRG1 effect is also maintained in old rats, suggesting that the NRG1/ErbB signaling pathway might represent a promising therapeutic target in insulin resistance states.

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Keywords : Ageing, ErbB, Glucose homoeostasis, Liver, NRG1, Skeletal muscle

Abbreviations : NRG1, ErbB, OGTT, AUC, HIRI, MISI, VEH